Characterization of Sexual Dimorphism in the Brain

大脑性别二态性的表征

• 批准号: 10166218
• 负责人: Nirao Mahesh Shah
• 金额: $ 9.01万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10166218
• 关键词: Androgens; Animals; Aromatase; Brain; Brain region; Cells; Diagnostic; Disease; Enzymes; Estrogens; Female; Fiber; Functional disorder; Future; Goals; Health; Heart; Hypothalamic structure; Label; Light; Link; Medial; Mental disorders; Microscopic; Molecular; Nerve Degeneration; Neurologic; Neuronal Dysfunction; Neurons; Partner in relationship; Pathway interactions; Photometry; Physiological; Physiology; Regulation; Reproductive Behavior; Research; Rewards; Rodent; Social Interaction; Stress; Structure of terminal stria nuclei of preoptic region; Testing; Testosterone; Therapeutic; Work; brain behavior; insight; mature animal; neural circuit; parent project; response; sex; sexual dimorphism; stressor

Project Summary Social interactions are powerfully modulated by internal physiological state and future goals. The goal of our project is a functional and molecular characterization of the mammalian bed nucleus of the stria terminalis (BNST), with a focus on its medial division posteromedial compartment (BNSTmpm). The BNSTmpm is sexually dimorphic across many mammalian species, and it has been implicated in a diversity of social interactions in both sexes and physiological responses. Consistent with these observations, BNSTmpm neurons express the enzyme aromatase that converts testosterone or related androgens into estrogens; aromatase activity is essential for wildtype sexual differentiation of the brain and behavior in both sexes in rodents and many other animals. However, the function of aromatase in different brain regions in adult animals remains poorly characterized. The research goals of the diversity supplement fit within the goals of the parent project, and in particular they are focused on a subset of the specific aims. We have identified a small subset of BNSTmpm neurons that are activated upon mating in females. In aim 1 of the supplement, we will use FosTrap to label these neurons and use fiber photometry to understand the specific components of mating that activate these cells. We will next use chemogenetic actuators to test if these mating-activated BNSTmpm neurons are necessary or sufficient for female reproductive behaviors. In aim 2 of the supplement, we will specifically delete aromatase in BNSTmpm neurons to test its functional contribution to sexually dimorphic social interactions and physiology in both sexes. In summary, the studies proposed for the diversity supplement fit within the overarching goals of the parent project. Health Relatedness: Neurodegenerative and psychiatric conditions often reflect dysfunction of neural circuitry at a gross or microscopic level, and these remain poorly understood and therapeutically intractable. The BNST is a critical node linking amygdalar, hypothalamic, and cortical networks in the regulation of social interactions, response to various stressors, and reward pathways. Our proposed studies will shed light on the connectivity and functions of a subset of BNST neurons in the two sexes, thereby leading to an advance in basic scientific understanding of this region and the neural circuits within which it functions in health, and it may ultimately provide insights into future therapeutic or diagnostic applications for mental illness and common neurodegenerative conditions.

项目摘要 社会互动是由内部生理状态和未来目标强大调节的。我们的目标 项目是Stria末端的哺乳动物床核的功能和分子表征 （BNST），重点是其内侧分裂后内侧室（BNSTMPM）。 BNSTMPM是性的 许多哺乳动物物种的二态，它与社会互动的多样性有关 性别和生理反应。与这些观察结果一致，BNSTMPM神经元表达 将睾丸激素或相关雄激素转化为雌激素的酶芳香酶；芳香酶活性是 啮齿动物和许多其他男女的野生型对大脑性和行为的性别分化至关重要 动物。但是，成年动物不同大脑区域中芳香酶的功能仍然很差 特征。多样性补充的研究目标符合父项目的目标，并在 特别是它们专注于特定目的的子集。我们已经确定了一小部分BNSTMPM 在女性交配后激活的神经元。在补充剂的目标1中，我们将使用fostrap标记 这些神经元并使用纤维光度法来了解激活这些的特定成分 细胞。接下来，我们将使用化学发生执行器来测试这些交配激活的BNSTMPM神经元是否是 对于女性生殖行为的必要或足够。在补充剂的AIM 2中，我们将特别删除 BNSTMPM神经元中的芳香化酶测试其对性二态社交互动的功能贡献和 性别的生理学。总而言之，提出了针对多样性补充的研究 父项目的总体目标。 健康相关性：神经退行性和精神疾病通常反映神经回路的功能障碍 在总体或显微镜水平上，这些理解和治疗方面的理解还不足。 Bnst 是在社会互动调节中连接杏仁核，下丘脑和皮质网络的关键节点， 对各种压力源的反应和奖励途径。我们提出的研究将阐明连通性 和两个性别中BNST神经元子集的功能，从而导致基本科学的进步 了解该区域以及其在健康中发挥作用的神经回路，最终可能 提供有关精神疾病和常见的未来治疗或诊断应用的见解 神经退行性条件。